High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains

Marius Schwabenland; Dilara Hasavci; Sibylle Frase; Katharina Wolf; Nikolaus Deigendesch; Joerg M Buescher; Kirsten D Mertz; Benjamin Ondruschka; Hermann Altmeppen; Jakob Matschke; Markus Glatzel; Stephan Frank; Robert Thimme; Juergen Beck; Jonas A Hosp; Thomas Blank; Bertram Bengsch; Marco Prinz

doi:10.1007/s00401-024-02770-6

High throughput spatial immune mapping reveals an innate immune scar in post-COVID-19 brains

Acta Neuropathol. 2024 Jul 25;148(1):11. doi: 10.1007/s00401-024-02770-6.

Authors

Marius Schwabenland¹, Dilara Hasavci¹, Sibylle Frase², Katharina Wolf^{2

3}, Nikolaus Deigendesch⁴, Joerg M Buescher⁵, Kirsten D Mertz^{6

7}, Benjamin Ondruschka⁸, Hermann Altmeppen⁹, Jakob Matschke⁹, Markus Glatzel⁹, Stephan Frank¹⁰, Robert Thimme¹¹, Juergen Beck³, Jonas A Hosp², Thomas Blank¹, Bertram Bengsch^{11

12}, Marco Prinz^{13

14}

Affiliations

¹ Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany.
² Department of Neurology and Neuroscience, University Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
³ Department of Neurosurgery, University Medical Center Freiburg, Freiburg, Germany.
⁴ Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁵ Max Planck Institute for Immunobiology and Epigenetics, 79108, Freiburg, Germany.
⁶ Institute of Pathology, Cantonal Hospital Baselland, Liestal, Switzerland.
⁷ University of Basel, Basel, Switzerland.
⁸ Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁹ Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁰ Division of Neuropathology, Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland.
¹¹ Clinic for Internal Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Disease, Faculty of Medicine, University Medical Center Freiburg, Freiburg, Germany.
¹² Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
¹³ Institute of Neuropathology, Faculty of Medicine, University of Freiburg, Breisacher Str. 64, 79106, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.
¹⁴ Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany. marco.prinz@uniklinik-freiburg.de.

Abstract

The underlying pathogenesis of neurological sequelae in post-COVID-19 patients remains unclear. Here, we used multidimensional spatial immune phenotyping and machine learning methods on brains from initial COVID-19 survivors to identify the biological correlate associated with previous SARS-CoV-2 challenge. Compared to healthy controls, individuals with post-COVID-19 revealed a high percentage of TMEM119⁺P2RY12⁺CD68⁺Iba1⁺HLA-DR⁺CD11c⁺SCAMP2⁺ microglia assembled in prototypical cellular nodules. In contrast to acute SARS-CoV-2 cases, the frequency of CD8⁺ parenchymal T cells was reduced, suggesting an immune shift toward innate immune activation that may contribute to neurological alterations in post-COVID-19 patients.

Keywords: COVID-19; Imaging mass cytometry; Long-COVID; Microglia; Neuro-long-COVID-19; PACS; PCC; Post-COVID condition; Post-acute COVID syndrome; SARS-CoV-2.

MeSH terms

Adult
Aged
Brain* / immunology
Brain* / pathology
CD8-Positive T-Lymphocytes / immunology
COVID-19* / immunology
Cicatrix / immunology
Cicatrix / pathology
Female
Humans
Immunity, Innate* / immunology
Machine Learning
Male
Microglia / immunology
Microglia / pathology
Middle Aged
SARS-CoV-2 / immunology